Abstract CT108: Immunogenicity of Poly-ICLC matured dendritic cells as an adjuvant for NY-ESO-1 and Melan-A-MART-1 peptide vaccination compared to Montanide® ISA-51 VG, in study subjects with melanoma in complete clinical remission but at high risk of disease recurrence
Authors: Mansi Saxena, Ashleih Burke, Anna Pavlick, Ana Blazquez, Gustavo Gimenez, Marcia Meseck, Michael Donovan, Denise Rodriguez, Mireia Castillo-Martin, Tin Htwe Thin, Rachel Sabado, John Mandeli, Sacha Gnjatic, Philip Friedlander, Nina Bhardwaj
Journal: Cancer Research (2022)

Abstract Background: Dendritic cells (DCs) play a critical role in anti-tumor immune response. However, tumor-induced immunosuppression promotes DC dysfunction and T cell exhaustion resulting in evasion of tumor immunity. In this study, we aimed to compare two approaches for engaging DCs and inducing an immune response to tumor antigens in the absence of tumor (melanoma) Methods: This is a Phase II open-label, randomized, two-arm study to compare Arm A: Poly-ICLC-matured DC+PolyICLC to Arm B: Montanide ISA-51-VG+Poly-ICLC, as adjuvants for NY-ESO-1 and Melan-A/MART-1 long peptides in patients with melanoma in complete clinical remission but at high risk of disease recurrence (NCT02334735). Each arm also received helper peptide, keyhole limpet hemocyanin (KLH) with the first vaccine and Poly-ICLC on day 2 of each vaccine. 36 patients were consented and randomized. Of these, 31 subjects received treatment, 16 in Arm A and 15 in Arm B. Immunohistochemistry (IHC) was used to determine expression of NY-ESO-1 and Melan-A/MART-1 and to determine the immune infiltrate landscape in the primary tumors. Humoral responses, TCR clonality, and inflammatory pathways were assessed by ELISA, bulk TCR sequencing, and Olink, respectively. Functional T-cell responses were investigated ex-vivo by interferon (IFN)-g enzyme-linked immunospot assay (ELISPOT) and after expansion by intracellular cytokine staining. Results: Arm B induced a stronger humoral response vs Arm A against both Melan-A/MART-1 and NY-ESO-1. A stronger ex vivo IFN-g response as well as expanded CD4+ T cell response against NY-ESO-1 was also induced in Arm B. However, the response to Melan-A/MART-1, as measured by ex vivo ELISPOT and expanded CD4+T cell assay, was comparable in both arms. Interestingly, while similar proportions of patients in each arm displayed a CD8+ T cell response to NYESO-1, more patients in Arm A vs Arm B responded with a CD8+ T cell response to Melan-A/MART-1 (9/16 responders in Arm A vs 4/14 in Arm B). Melan-A expression was observed in 81% of the patients but did not correlate with antigen specific immune response. TCR sequencing, Olink analysis and evaluation of NY-ESO-1 expression and immune infiltrates in the primary tumors is ongoing. Conclusion: This trial reached the primary endpoint of safety and tolerability. Arm B induced a stronger antibody and CD4+ T cell response, especially to NY-ESO-1, whereas the Arm A vaccine appears to be more efficient at eliciting CD8+ T cell responses against MelanA/MART1. The seemingly enhanced CD8 T cell response in Arm A versus Arm B, could be attributed to frequency of specific HLA-I alleles in either arm or pre-existing immune response in select patients. A deeper investigation into correlation between HLA type and cellular immune response to vaccine is ongoing. Citation Format: Mansi Saxena, Ashleih Burke, Anna Pavlick, Ana Blazquez, Gustavo Gimenez, Marcia Meseck, Michael Donovan, Denise Rodriguez, Mireia Castillo-Martin, Tin Htwe Thin, Rachel Sabado, John Mandeli, Sacha Gnjatic, Philip Friedlander, Nina Bhardwaj. Immunogenicity of Poly-ICLC matured dendritic cells as an adjuvant for NY-ESO-1 and Melan-A-MART-1 peptide vaccination compared to Montanide® ISA-51 VG, in study subjects with melanoma in complete clinical remission but at high risk of disease recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT108.